title: An insight into potential of nanoparticles-assisted chemotherapy of cancer using gemcitabine and its fatty acid prodrug:a comparative study.
abstract: Gemcitabine (dFdC) mediated cancer treatment faces obstacles, due to its high hydrophilicity. A valuable strategy was executed by synthesizing lipophilic fatty acid derivative of dFdC i.e., 4-(N)-stearoyl gemcitabine (C18dFdC), built-in into polymeric poly-lactic-co-glycolic acid nanoparticles (PLGA NPs) and compared with that of parent drug. Encapsulation of derivative within NPs was higher (68.24 +/- 3.64%) than dFdC and showed comparatively sustained drug release (19.87 +/- 1.73% within 12 hours), with a proof of increased biological half life. The cytotoxicity and flow cytometric analysis displayed enhanced MCF-7 cell inhibition by C18dFdC-NPs with higher uptake compared to dFdC-NPs. Interestingly, like gemcitabine, C18dFdC-NPs did not induce appreciable differences in blood parameters and in vivo tissue toxicity study demonstrating safe use of derivative at 40 mg/kg dose. In conclusion, the preclinical data obtained in vitro and in vivo demonstrate the C18dFdC-nanocarrier as an advantageous and promising delivery system for cancer treatment along with the potential to improve the clinical outcome of gemcitabine chemotherapy.
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, UP 226001, India.
authors.forename: A
authors.initials: A
authors.lastname: Gupta
authors.forename: S
authors.initials: S
authors.lastname: Asthana
authors.forename: R
authors.initials: R
authors.lastname: Konwar
authors.forename: M K
authors.initials: MK
authors.lastname: Chourasia
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016503:Drug Delivery Systems; D005227:Fatty Acids / Q000008:administration & dosage / Q000737:chemistry; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D053758:Nanoparticles; D009369:Neoplasms / Q000188:drug therapy*; D011355:Prodrugs / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D005227:Fatty Acids; D011355:Prodrugs; D003841:Deoxycytidine; D000093542:Gemcitabine